Alcohol-induced activation of the HPA axis results in elevated circulating glucocorticoids and it has been suggested that this may contribute to amplified motivation to drink through an interaction with brain reward circuitry (Piazza and Le Moal, 1997; Uhart and Wand, 2009). Central and systemic administration of corticosterone has been shown to increase alcohol consumption, whereas adrenalectomy or administration of a corticosteroid synthesis inhibitor (i.e., metyrapone) decreased alcohol intake in rodents (Fahlke et al., 1995; Fahlke et al., 1996). Likewise, a glucocorticoid receptor antagonist (i.e., mifepristone) reduced alcohol self-administration behavior in rats (Koenig and Olive, 2004). Furthermore, mifepristone administered systemically or into the central nucleus (but not the basolateral nucleus) of the amygdala attenuated stress-induced reinstatement of alcohol seeking behavior (Simms et al., 2012).
